Project description:Background. Accumulating evidence indicates that CFTR modulators can be effective for CF sufferers. However, in vivo the microRNAs that regulate CFTR are increased in the CF lung milieu and this can nullify the beneficial effects of CFTR modulators. Methods. A panel of target site blockers (TSBs) designed against the CFTR 3’untranslated region (UTR) were tested for their ability to increase CFTR expression by CFTR 3’UTR luciferase assay and western blot. The effect of two lead TSBs on CFTR activity were tested alone or in combination with selected CFTR modulators in four separate p.Phe508del/p.Phe508del in vitro and ex vivo models (CFBE41o-, Cufi-1, primary bronchial epithelial cells, iPSC-derived lung organoids). Respirable poly-lactic-co-glycolic acid (PLGA) nanoparticles encapsulating the TSBs were formulated and tested. Findings. TSBs that target the miR-145-5p or miR-223-3p binding sites at positons 298-305 and 166-173 in the CFTR 3’UTR, respectively, increased CFTR expression and CFTR anion channel activity, and enhance the effects of Lumacaftor/Ivacaftor or Lumacftor/Tezacaftor in CF BECs. PLGAs encapsulating the TSBs promote CFTR expression in primary BECs and retain their biophysical characteristics following nebulization. Interpretation. Alone or in combination with CFTR modulators, CFTR-targeting TSBs encapsulated in PLGA nanoparticles and nebulized to the lung could overcome microRNA-mediated inhibition of CFTR in CF bronchial epithelium. This strategy represents a promising drug-device combination therapy for the treatment for CFTR dysfunction in the lung.

2019-03-27 | GSE128861 | GEO

Linc01133 contributes to gastric cancer growth by enhancing YES1-dependent YAP1 nuclear translocation via sponging miR-145-5p.

Project description: Not available

| S-EPMC8752595 | biostudies-literature

circPTN sponges miR-145-5p/miR-330-5p to promote proliferation and stemness in glioma.

Project description: Not available

| S-EPMC6737709 | biostudies-literature

Combination of circulating miR-145-5p/miR-191-5p as biomarker for breast cancer detection.

Project description: Not available

| S-EPMC7749656 | biostudies-literature

Epigenetic silencing of miR-145-5p contributes to brain metastasis.

Project description: Not available

| S-EPMC4742098 | biostudies-literature

Identification of miR-145 targets using SILAC

Project description:miR-145 is downregulated in multiple cancers. The introduction of miR-145 could alleviate the tumor burden in the pancreatic cancer mouse model. However, how miR-145 mediates the tumor suppression is still an open question. In this study, we aimed to identify the targets of miR-145 using a SILAC approach.

2014-10-28 | PXD001260 | Pride

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